Session Information

current session info


─ Session info ───────────────────────────────────────────────────────────────
 setting  value                       
 version  R version 3.6.1 (2019-07-05)
 os       macOS High Sierra 10.13.6   
 system   x86_64, darwin15.6.0        
 ui       X11                         
 language (EN)                        
 collate  en_US.UTF-8                 
 ctype    en_US.UTF-8                 
 tz       America/Los_Angeles         
 date     2020-02-20                  

─ Packages ───────────────────────────────────────────────────────────────────
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[1] /Library/Frameworks/R.framework/Versions/3.6/Resources/library


Aim

The aim of this study is to obtain the Reliability estimates of the OCTA measurements.

Reliability incorporates:

  • Repeatability - How reliable are repeated measures on the same day (Intra-Visit)

  • Reproducibility - How reliable are repeated measures over multiple visits (Inter-Visit)

Data

This data was taken from a clean dataset that Jae emailed out on January 16th, 2020.

Jae organized the retina by six different methods. He created OCTA variable scores for the overall image, 2 hemifields, 4 quadrants, 6 sectors, 12 clock hours, and an annular ring.

Annular image scoring was also assessed, and ICC’s were similar, but slightly lower than global. Results for annular image scoring are not shown. For now, only the overall “global” image scoring will be shown.

Zeiss commercial vessel area density and flux variables are also shown for the global image scoring.

Note to Dom: The analysis was originally built with the global data. Towards the end of our work, we decided annulus would be a better data to use. I had already built the analysis using global data, so I just “trojan horsed” the annulus excel data into the global analysis that already exists. This is a bit of a hack, but saves an immense amount of time.

Data Wrangling

Rename Variables

This section will rename the variables to match the dictionary

Label Variables

This section will label variables appropriately.

Data Dictionary

Variable Label
ptid Patient Identification
Sociodemographic Variables
age Age
female Sex
Systemic Clinical Variables
htn_dx Hypertension Diagnosis
dm_dx Diabetes Mellitus Diagnosis
nro_dx Optic Neuropathy
Ophthalmic Clinical Variables
dr_dx Diabetic Retinopathy Diagnosis, Ordinal
dr_dx_bin Diabetic Retinopathy Diagnosis, Binary
glc_sus_dx Glaucoma Suspect Diagnosis
glc_dx Glaucoma Diagnosis, Ordinal
glc_dx_bin Glaucoma Diagnosis, Binary
glc_dx_bin_people Glaucoma Diagnosis Laterality, Ordinal
OCT Angiography Variables
surg_proc_glaucoma Surgical Procedure for Glaucoma
surg_proc_catextract Surgical Procedure for Cataract Extraction
eyeid Eye Identification
eye_imaged Eye Imaged
time_stamp Exam Date and Time
name_last Last Name
name_first First Name
image_area Image Area
image_method Image Method
image_size Image Size
signal_strength Signal Strength
v_diameter Vessel Diameter (units?)
v_area_density Vessel Area Density
v_skeleton_density Vessel Skeleton Density (units?)
v_perimeter_index Vessel Perimeter Index (units?)
v_complexity_index Vessel Complexity Index (units?)
flow_impair_zone Flow Impairment Zone (units?)
flux Flux
zeiss_v_area_density Vessel Area Density, Zeiss
zeiss_flux Flux, Zeiss

Single Eye Participation

Venugopal (2019) et al. ran the analysis including all eyes.1 Then they re-ran the analysis after selecting only a single eye randomly from each individual. They conclude minimal difference in the findings, and they report only the analysis that includes all eyes:

“The entire analysis was repeated considering one eye per subject (one eye was randomly chosen from subjects contributing both eyes for the primary analysis) and all the results were similar to the primary analysis.”1

The following results are for a single eye—chosen at random—from each participant.

Later, towards the bottom of the analysis, the reliability statistics have been repeated for both eyes using linear mixed effects models.

Subsetting Cohorts

Intra-Visit Data

Intra-visit data was restricted to all measurements of the same eye that occurred on the same day. Some people had multiple measurements on multiple days. Their first day was included only.

Inter-Visit Data

Inter-visit data was restricted to the first measurement of the day for each eye. If a patient had their right eye measured:

  • 3 times on Monday

  • 5 times on Wednesday, and

  • 2 times on Friday,

Then they would have three observations in this dataset:

  • The first measurement from Monday,

  • The first measurement from Wednesday, and

  • The first measurement from Friday.

Data Flow Chart

This tallies how many participants, how many eyes, and how many measurements are included in the two data sets.

For repeatability statistics, normal and glaucoma groups may sum to greater than the total number of participants in the study because some participants have both eyes normal or both eyes with glaucoma, but some patients have unilateral glaucoma.

Both Eyes

dataset n_participants n_eyes n_measurements
Annular Data - Intra-Visit - Both Eyes
Intra-Visit 149 244 644
Intra-Visit, Normal 73 118 321
Intra-Visit, Glaucoma 86 126 323
Annular Data - Inter-Visit - Both Eyes
Inter-Visit 148 243 628
Inter-Visit, Normal 72 117 256
Inter-Visit, Glaucoma 86 126 372
Annular Data - Inter-Visit - Both Eyes - Restrict 1 Year
Inter-Visit, 1 Year 103 165 401
Inter-Visit, 1 Year, Normal 44 69 143
Inter-Visit, 1 Year, Glaucoma 67 96 258
Annular Data - Inter-Visit - Both Eyes - Restrict 6 Months
Inter-Visit, 6 Months 67 107 254
Inter-Visit, 6 Months, Normal 23 32 68
Inter-Visit, 6 Months, Glaucoma 52 75 186

One Eye, Random

dataset n_participants n_eyes n_measurements
Annular Data - Intra-Visit - One Eye, Random
Intra-Visit 149 149 382
Intra-Visit, Normal 68 68 180
Intra-Visit, Glaucoma 81 81 202
Annular Data - Inter-Visit - One Eye, Random
Inter-Visit 148 148 376
Inter-Visit, Normal 67 67 151
Inter-Visit, Glaucoma 81 81 225
Annular Data - Inter-Visit - One Eye, Random - Restrict 1 Year
Inter-Visit, 1 Year 102 102 246
Inter-Visit, 1 Year, Normal 40 40 85
Inter-Visit, 1 Year, Glaucoma 62 62 161
Annular Data - Inter-Visit - One Eye, Random - Restrict 6 Months
Inter-Visit, 6 Months 67 67 157
Inter-Visit, 6 Months, Normal 19 19 42
Inter-Visit, 6 Months, Glaucoma 48 48 115

Table 1: Summary Statistics

All table 1 data is shown, but publish only the Table 1 for the Intra-Visit.

For repeatability statistics, normal and glaucoma groups may sum to greater than the total number of participants in the study because some participants have both eyes normal or both eyes with glaucoma, but some patients have unilateral glaucoma.

Intra-Visit, Both Eyes OCTA Summary Statistics

Variables in intra-visit dataset

Intra-Visit

Overall
n 149
Sociodemographic Variables
age (mean (SD)) 56.97 (16.10)
Sex = Male (%) 72 (48.3)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 43 (28.9)
Diabetes Mellitus Diagnosis = Yes (%) 17 (11.4)
Optic Neuropathy = Yes (%) 1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 76 (51.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 60 (40.3)
Glaucoma, Bilateral 71 (47.7)
Glaucoma, Unilateral 18 (12.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 28 (18.8)
Surgical Procedure for Glaucoma (%)
None 103 (69.1)
Laser 24 (16.1)
Minimally Invasive Glaucoma Surgery 2 ( 1.3)
Filter 20 (13.4)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.28 (0.68)

Intra-Visit, Normal

Overall
n 73
Sociodemographic Variables
age (mean (SD)) 51.68 (16.15)
Sex = Male (%) 35 (47.9)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 16 (21.9)
Diabetes Mellitus Diagnosis = Yes (%) 3 ( 4.1)
Optic Neuropathy = Yes (%) 1 ( 1.4)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 60 (82.2)
Glaucoma, Bilateral 0 ( 0.0)
Glaucoma, Unilateral 13 (17.8)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 9 (12.3)
Surgical Procedure for Glaucoma (%)
None 67 (91.8)
Laser 6 ( 8.2)
Minimally Invasive Glaucoma Surgery 0 ( 0.0)
Filter 0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.43 (0.60)

Intra-Visit, Glaucoma

Overall
n 86
Sociodemographic Variables
age (mean (SD)) 61.82 (13.84)
Sex = Male (%) 42 ( 48.8)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 29 ( 33.7)
Diabetes Mellitus Diagnosis = Yes (%) 14 ( 16.3)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 86 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 0 ( 0.0)
Glaucoma, Bilateral 71 ( 82.6)
Glaucoma, Unilateral 15 ( 17.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 4.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 22 ( 25.6)
Surgical Procedure for Glaucoma (%)
None 46 ( 53.5)
Laser 18 ( 20.9)
Minimally Invasive Glaucoma Surgery 2 ( 2.3)
Filter 20 ( 23.3)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.12 (0.75)

Inter-Visit, Both Eyes OCTA Summary Statistics

Variables in inter-visit dataset

All

Inter-Visit

Overall
n 148
Sociodemographic Variables
age (mean (SD)) 57.19 (15.92)
Sex = Male (%) 71 (48.0)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 43 (29.1)
Diabetes Mellitus Diagnosis = Yes (%) 17 (11.5)
Optic Neuropathy = Yes (%) 1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 76 (51.4)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 59 (39.9)
Glaucoma, Bilateral 71 (48.0)
Glaucoma, Unilateral 18 (12.2)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 28 (18.9)
Surgical Procedure for Glaucoma (%)
None 102 (68.9)
Laser 24 (16.2)
Minimally Invasive Glaucoma Surgery 2 ( 1.4)
Filter 20 (13.5)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.26 (0.65)

Inter-Visit, Normal

Overall
n 72
Sociodemographic Variables
age (mean (SD)) 52.07 (15.92)
Sex = Male (%) 34 (47.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 16 (22.2)
Diabetes Mellitus Diagnosis = Yes (%) 3 ( 4.2)
Optic Neuropathy = Yes (%) 1 ( 1.4)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 59 (81.9)
Glaucoma, Bilateral 0 ( 0.0)
Glaucoma, Unilateral 13 (18.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 9 (12.5)
Surgical Procedure for Glaucoma (%)
None 66 (91.7)
Laser 6 ( 8.3)
Minimally Invasive Glaucoma Surgery 0 ( 0.0)
Filter 0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.45 (0.60)

Inter-Visit, Glaucoma

Overall
n 86
Sociodemographic Variables
age (mean (SD)) 61.82 (13.84)
Sex = Male (%) 42 ( 48.8)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 29 ( 33.7)
Diabetes Mellitus Diagnosis = Yes (%) 14 ( 16.3)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 86 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 0 ( 0.0)
Glaucoma, Bilateral 71 ( 82.6)
Glaucoma, Unilateral 15 ( 17.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 4.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 22 ( 25.6)
Surgical Procedure for Glaucoma (%)
None 46 ( 53.5)
Laser 18 ( 20.9)
Minimally Invasive Glaucoma Surgery 2 ( 2.3)
Filter 20 ( 23.3)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.08 (0.67)

1 Year

These are the participants we will be using for inter-visit glaucoma

Inter-Visit

Overall
n 103
Sociodemographic Variables
age (mean (SD)) 56.93 (15.64)
Sex = Male (%) 52 (50.5)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 29 (28.2)
Diabetes Mellitus Diagnosis = Yes (%) 14 (13.6)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 59 (57.3)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 33 (32.0)
Glaucoma, Bilateral 54 (52.4)
Glaucoma, Unilateral 16 (15.5)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 3.9)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 19 (18.4)
Surgical Procedure for Glaucoma (%)
None 70 (68.0)
Laser 14 (13.6)
Minimally Invasive Glaucoma Surgery 1 ( 1.0)
Filter 18 (17.5)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.20 (0.64)

Inter-Visit, Normal

Overall
n 44
Sociodemographic Variables
age (mean (SD)) 51.17 (14.47)
Sex = Male (%) 20 (45.5)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 7 (15.9)
Diabetes Mellitus Diagnosis = Yes (%) 1 ( 2.3)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 0 ( 0.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 33 (75.0)
Glaucoma, Bilateral 0 ( 0.0)
Glaucoma, Unilateral 11 (25.0)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 0 ( 0.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 5 (11.4)
Surgical Procedure for Glaucoma (%)
None 42 (95.5)
Laser 2 ( 4.5)
Minimally Invasive Glaucoma Surgery 0 ( 0.0)
Filter 0 ( 0.0)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.45 (0.58)

Inter-Visit, Glaucoma

Overall
n 67
Sociodemographic Variables
age (mean (SD)) 61.16 (14.45)
Sex = Male (%) 35 ( 52.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 23 ( 34.3)
Diabetes Mellitus Diagnosis = Yes (%) 13 ( 19.4)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 67 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 0 ( 0.0)
Glaucoma, Bilateral 54 ( 80.6)
Glaucoma, Unilateral 13 ( 19.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 6.0)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 16 ( 23.9)
Surgical Procedure for Glaucoma (%)
None 36 ( 53.7)
Laser 12 ( 17.9)
Minimally Invasive Glaucoma Surgery 1 ( 1.5)
Filter 18 ( 26.9)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.02 (0.64)

6 Months

These are the participants we will be using for inter-visit normal

Inter-Visit

Overall
n 67
Sociodemographic Variables
age (mean (SD)) 57.60 (15.78)
Sex = Male (%) 35 (52.2)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 17 (25.4)
Diabetes Mellitus Diagnosis = Yes (%) 9 (13.4)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 44 (65.7)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 13 (19.4)
Glaucoma, Bilateral 43 (64.2)
Glaucoma, Unilateral 11 (16.4)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 3 ( 4.5)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 13 (19.4)
Surgical Procedure for Glaucoma (%)
None 41 (61.2)
Laser 9 (13.4)
Minimally Invasive Glaucoma Surgery 1 ( 1.5)
Filter 16 (23.9)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.10 (0.65)

Inter-Visit, Normal

Inter-Visit, Glaucoma

Overall
n 52
Sociodemographic Variables
age (mean (SD)) 60.51 (14.74)
Sex = Male (%) 27 ( 51.9)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 16 ( 30.8)
Diabetes Mellitus Diagnosis = Yes (%) 9 ( 17.3)
Optic Neuropathy = Yes (%) 0 ( 0.0)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 52 (100.0)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 0 ( 0.0)
Glaucoma, Bilateral 43 ( 82.7)
Glaucoma, Unilateral 9 ( 17.3)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 3 ( 5.8)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 13 ( 25.0)
Surgical Procedure for Glaucoma (%)
None 27 ( 51.9)
Laser 8 ( 15.4)
Minimally Invasive Glaucoma Surgery 1 ( 1.9)
Filter 16 ( 30.8)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 8.98 (0.64)

Exploratory Data Analysis

Scatter Plots

Scatter plots of OCTA variables by Subject ID for about 10 individuals randomly sampled. These are separated by intra- and inter-visit data sets, and are useful for understanding the data better.

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Spaghetti Plots

Spaghetti plots of OCTA variables for about 10 individuals randomly sampled.

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Bland-Altman Plots

Coding of Bland-Altman (BA) plots is explained in this blog post.

Intra-Visit Bland-Altman Plots

Intra-Visit Bland-Altman Plots of OCTA Variables

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Outliers

Assess some of the observations outside of expected limits.

eyeid ptid signal_strength female eye_imaged image_area image_size image_method exam_date time_stamp v_diameter v_area_density v_skeleton_density v_perimeter_index v_complexity_index flow_impair_zone flux zeiss_v_area_density zeiss_flux age htn_dx dm_dx nro_dx dr_dx glc_sus_dx glc_dx surg_proc_glaucoma surg_proc_catextract glc_dx_bin dr_dx_bin glc_dx_bin_people n_msr_day order_obs
11 1226815 9 Female Left ONH 6x6 Angiography 2019-10-25 2019-10-25 12:41:03 30.29640 0.1370255 0.04522833 0.1273263 2149.126 19.5292 0.04483744 0.357 0.255 74.0 No No No None None Severe Laser No Glaucoma No Glaucoma, Bilateral 2 1
11 1226815 9 Female Left ONH 6x6 Angiography 2019-10-25 2019-10-25 12:42:40 28.69309 0.1573387 0.05483507 0.1448204 2425.982 17.3898 0.05181468 0.358 0.262 74.0 No No No None None Severe Laser No Glaucoma No Glaucoma, Bilateral 2 2
18 1380225 10 Female Left ONH 6x6 Angiography 2019-03-20 2019-03-20 11:25:51 25.34368 0.2927191 0.11549981 0.2730479 4419.194 5.8646 0.09498110 0.391 0.312 59.5 No No No None Severe None None No Normal No Normal, Bilateral 3 1
18 1380225 10 Female Left ONH 6x6 Angiography 2019-03-20 2019-03-20 11:26:24 25.93677 0.2808006 0.10826349 0.2626908 4354.005 6.0290 0.09104601 0.387 0.308 59.5 No No No None Severe None None No Normal No Normal, Bilateral 3 2
18 1380225 10 Female Left ONH 6x6 Angiography 2019-03-20 2019-03-20 11:26:54 25.57051 0.2913801 0.11395163 0.2715677 4492.345 6.0963 0.09378992 0.391 0.314 59.5 No No No None Severe None None No Normal No Normal, Bilateral 3 3
21 138721 8 Female Right ONH 6x6 Angiography 2018-03-23 2018-03-23 12:35:54 24.11877 0.3366931 0.13959797 0.3099195 4770.301 6.6043 0.12174832 0.415 0.354 71.0 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 3 1
21 138721 9 Female Right ONH 6x6 Angiography 2018-03-23 2018-03-23 12:36:56 24.79561 0.3413820 0.13767841 0.3139906 5034.907 6.1268 0.12247720 0.407 0.358 71.0 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 3 2
21 138721 7 Female Right ONH 6x6 Angiography 2018-03-23 2018-03-23 12:44:53 24.65734 0.3008142 0.12199783 0.2776850 4386.743 7.7867 0.10278178 0.398 0.331 71.0 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 3 3
39 1722883 10 Male Right ONH 6x6 Angiography 2019-08-09 2019-08-09 10:34:25 25.54585 0.3697135 0.14472546 0.3375627 5470.442 4.0666 0.13764308 0.403 0.371 62.8 No No No None Severe None None No Normal No Normal, Bilateral 3 1
39 1722883 10 Male Right ONH 6x6 Angiography 2019-08-09 2019-08-09 10:35:07 25.24136 0.3861241 0.15297278 0.3529328 5781.427 3.6101 0.13843919 0.408 0.375 62.8 No No No None Severe None None No Normal No Normal, Bilateral 3 2
39 1722883 10 Male Right ONH 6x6 Angiography 2019-08-09 2019-08-09 10:35:44 24.32060 0.4155198 0.17085094 0.3791646 6189.701 2.6544 0.15392797 0.427 0.389 62.8 No No No None Severe None None No Normal No Normal, Bilateral 3 3
40 1755703 9 Female Left ONH 6x6 Angiography 2019-01-23 2019-01-23 08:58:07 25.44699 0.3225155 0.12674015 0.2954372 4904.017 7.0431 0.11022962 0.423 0.343 60.0 No No No None Severe None None No Normal No Normal, Bilateral 2 1
40 1755703 9 Female Left ONH 6x6 Angiography 2019-01-23 2019-01-23 08:58:33 25.48799 0.2949723 0.11572993 0.2713770 4545.290 9.9067 0.10021295 0.422 0.329 60.0 No No No None Severe None None No Normal No Normal, Bilateral 2 2
58 2083485 8 Male Right ONH 6x6 Angiography 2019-06-05 2019-06-05 11:04:06 26.75168 0.2667196 0.09970197 0.2453661 3983.900 10.8190 0.09260453 0.381 0.323 68.0 Yes No No None Moderate None None Yes Normal No Normal, Bilateral 3 1
58 2083485 8 Male Right ONH 6x6 Angiography 2019-06-05 2019-06-05 11:04:42 26.42129 0.2593079 0.09814356 0.2388267 3917.684 10.5598 0.09140341 0.387 0.319 68.0 Yes No No None Moderate None None Yes Normal No Normal, Bilateral 3 2
58 2083485 8 Male Right ONH 6x6 Angiography 2019-06-05 2019-06-05 11:05:32 27.14406 0.2323210 0.08558813 0.2144602 3489.403 11.8333 0.08029139 0.368 0.310 68.0 Yes No No None Moderate None None Yes Normal No Normal, Bilateral 3 3
92 51313 10 Female Right ONH 6x6 Angiography 2019-10-04 2019-10-04 13:46:37 25.37820 0.2431212 0.09579924 0.2268217 3792.671 9.7405 0.07838918 0.377 0.296 65.4 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 2 1
92 51313 9 Female Right ONH 6x6 Angiography 2019-10-04 2019-10-04 13:49:13 25.35997 0.2507987 0.09889549 0.2331802 3850.294 9.1813 0.08112071 0.387 0.297 65.4 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 2 2
95 56867 10 Male Right ONH 6x6 Angiography 2019-09-06 2019-09-06 13:47:30 24.95075 0.3282209 0.13154753 0.3035419 5033.684 7.0176 0.11306028 0.413 0.339 83.0 Yes No No None Moderate None Laser Yes Normal No Normal, Bilateral 3 1
95 56867 10 Male Right ONH 6x6 Angiography 2019-09-06 2019-09-06 13:47:51 25.19313 0.3170639 0.12585328 0.2917371 4815.958 7.0559 0.11002868 0.412 0.338 83.0 Yes No No None Moderate None Laser Yes Normal No Normal, Bilateral 3 2
95 56867 10 Male Right ONH 6x6 Angiography 2019-09-06 2019-09-06 13:48:13 25.30722 0.3020664 0.11935978 0.2789155 4672.353 8.1056 0.10262727 0.409 0.329 83.0 Yes No No None Moderate None Laser Yes Normal No Normal, Bilateral 3 3
130 7005925 9 Female Left ONH 6x6 Angiography 2018-08-02 2018-08-02 09:15:19 26.99969 0.2754437 0.10201736 0.2530386 4119.877 9.5881 0.09242421 0.414 0.310 58.0 Yes No No None None Moderate Laser No Glaucoma No Glaucoma, Bilateral 2 1
130 7005925 10 Female Left ONH 6x6 Angiography 2018-08-02 2018-08-02 09:15:53 26.30913 0.2907589 0.11051634 0.2666798 4356.173 8.7396 0.09770604 0.416 0.315 58.0 Yes No No None None Moderate Laser No Glaucoma No Glaucoma, Bilateral 2 2
143 7131431 9 Male Left ONH 6x6 Angiography 2018-08-15 2018-08-15 09:41:56 24.21184 0.4091970 0.16900697 0.3747174 5942.869 1.4010 0.14646586 0.454 0.365 51.0 No No No None Mild None None No Normal No Normal, Bilateral 2 1
143 7131431 10 Male Left ONH 6x6 Angiography 2018-08-15 2018-08-15 09:43:08 24.20815 0.4025210 0.16627498 0.3689489 5702.549 1.8829 0.14140949 0.454 0.350 51.0 No No No None Mild None None No Normal No Normal, Bilateral 2 2
171 7258827 10 Female Left ONH 6x6 Angiography 2018-12-12 2018-12-12 10:06:49 24.84787 0.4359879 0.17546287 0.3953800 6290.749 2.3042 0.17096520 0.441 0.414 20.0 Yes No No None None Mild Filter No Glaucoma No Glaucoma, Bilateral 3 1
171 7258827 10 Female Left ONH 6x6 Angiography 2018-12-12 2018-12-12 10:07:14 24.99868 0.4291201 0.17165714 0.3905509 6230.003 2.6333 0.16776221 0.438 0.411 20.0 Yes No No None None Mild Filter No Glaucoma No Glaucoma, Bilateral 3 2
171 7258827 10 Female Left ONH 6x6 Angiography 2018-12-12 2018-12-12 10:07:36 24.88477 0.4121186 0.16561075 0.3765523 6076.072 3.5818 0.15629089 0.433 0.397 20.0 Yes No No None None Mild Filter No Glaucoma No Glaucoma, Bilateral 3 3
174 725907 8 Male Right ONH 6x6 Angiography 2019-02-27 2019-02-27 09:00:30 29.25085 0.1624065 0.05552199 0.1487154 2475.067 14.2008 0.05396190 0.360 0.272 46.0 No No No None None Severe Laser No Glaucoma No Glaucoma, Bilateral 3 1
174 725907 8 Male Right ONH 6x6 Angiography 2019-02-27 2019-02-27 09:00:54 28.14171 0.1786021 0.06346527 0.1635242 2731.644 12.8631 0.05996023 0.358 0.281 46.0 No No No None None Severe Laser No Glaucoma No Glaucoma, Bilateral 3 2
174 725907 9 Male Right ONH 6x6 Angiography 2019-02-27 2019-02-27 09:01:18 27.58670 0.2007703 0.07277793 0.1839710 3072.000 10.9801 0.06768001 0.356 0.293 46.0 No No No None None Severe Laser No Glaucoma No Glaucoma, Bilateral 3 3
183 7281737 9 Female Left ONH 6x6 Angiography 2019-02-08 2019-02-08 09:40:28 25.93341 0.2528107 0.09748458 0.2353340 3984.935 8.3944 0.08184594 0.380 0.301 72.3 No No No None None Moderate None Yes Glaucoma No Glaucoma, Unilateral 3 1
183 7281737 8 Female Left ONH 6x6 Angiography 2019-02-08 2019-02-08 09:40:59 26.26110 0.2393146 0.09112893 0.2231295 3744.725 9.8493 0.07699201 0.371 0.298 72.3 No No No None None Moderate None Yes Glaucoma No Glaucoma, Unilateral 3 2
183 7281737 9 Female Left ONH 6x6 Angiography 2019-02-08 2019-02-08 09:41:30 25.07638 0.3100368 0.12363701 0.2864197 4771.679 5.3852 0.10217958 0.403 0.320 72.3 No No No None None Moderate None Yes Glaucoma No Glaucoma, Unilateral 3 3
192 7349639 9 Female Right ONH 6x6 Angiography 2018-05-17 2018-05-17 07:12:52 27.55197 0.1913157 0.06943811 0.1778472 2944.142 14.1081 0.06679617 0.350 0.285 78.0 Yes No No None None Severe Filter Yes Glaucoma No Glaucoma, Bilateral 2 1
192 7349639 10 Female Right ONH 6x6 Angiography 2018-05-17 2018-05-17 07:13:22 28.78626 0.1813382 0.06299471 0.1685112 2775.510 15.2113 0.06136395 0.346 0.281 78.0 Yes No No None None Severe Filter Yes Glaucoma No Glaucoma, Bilateral 2 2
208 7519765 8 Male Left ONH 6x6 Angiography 2019-08-30 2019-08-30 15:30:14 27.20185 0.2107805 0.07748754 0.1948209 3237.692 12.4292 0.06973939 0.367 0.295 61.0 Yes No No None None Severe Laser Yes Glaucoma No Glaucoma, Bilateral 2 1
208 7519765 10 Male Left ONH 6x6 Angiography 2019-08-30 2019-08-30 15:32:55 25.39811 0.2800877 0.11027896 0.2571687 4292.763 8.2164 0.09770912 0.379 0.328 61.0 Yes No No None None Severe Laser Yes Glaucoma No Glaucoma, Bilateral 2 2
220 7618939 9 Male Right ONH 6x6 Angiography 2019-11-01 2019-11-01 10:00:51 24.31144 0.3621905 0.14897947 0.3345446 5352.807 2.8209 0.12682591 0.425 0.358 63.9 No No No None Mild None None Yes Normal No Glaucoma, Unilateral 2 1
220 7618939 9 Male Right ONH 6x6 Angiography 2019-11-01 2019-11-01 10:01:46 23.92392 0.3362092 0.14053265 0.3104898 5173.177 4.9099 0.11296480 0.416 0.344 63.9 No No No None Mild None None Yes Normal No Glaucoma, Unilateral 2 2
232 7685911 10 Male Left ONH 6x6 Angiography 2019-05-17 2019-05-17 09:36:40 24.43870 0.4260757 0.17434466 0.3894777 6321.509 1.9411 0.15991722 0.456 0.377 41.9 No No No None Mild None None No Normal No Normal, Bilateral 3 1
232 7685911 10 Male Left ONH 6x6 Angiography 2019-05-17 2019-05-17 09:37:09 24.15303 0.4292999 0.17774163 0.3924835 6372.214 1.6997 0.16470424 0.453 0.386 41.9 No No No None Mild None None No Normal No Normal, Bilateral 3 2
232 7685911 10 Male Left ONH 6x6 Angiography 2019-05-17 2019-05-17 09:37:41 24.34898 0.4349116 0.17861592 0.3974844 6497.414 1.3569 0.16220947 0.462 0.379 41.9 No No No None Mild None None No Normal No Normal, Bilateral 3 3

Inter-Visit Bland-Altman Plots

Inter-Visit Bland-Altman Plots of OCTA Variables

Vessel Area Density

Vessel Area Density, Zeiss

Vessel Diameter

Vessel Skeleton Density

Vessel Perimeter Index

Vessel Complexity Index

Flow Impairment Zone

Flux

Flux, Zeiss

Outliers

Assess some of the observations outside of expected limits.

eyeid ptid signal_strength female eye_imaged image_area image_size image_method exam_date time_stamp v_diameter v_area_density v_skeleton_density v_perimeter_index v_complexity_index flow_impair_zone flux zeiss_v_area_density zeiss_flux age htn_dx dm_dx nro_dx dr_dx glc_sus_dx glc_dx surg_proc_glaucoma surg_proc_catextract glc_dx_bin dr_dx_bin glc_dx_bin_people order_obs day_one diff_date ind_n_day n_exams
42 1787031 8 Female Right ONH 6x6 Angiography 2018-10-10 2018-10-10 10:45:55 25.09862 0.2859831 0.11394375 0.2634102 4329.615 10.3229 0.09907050 0.380 0.288 52.0 No No No None Severe None None Yes Normal No Normal, Bilateral 1 2018-10-10 0 days 1 3
42 1787031 9 Female Right ONH 6x6 Angiography 2019-04-10 2019-04-10 11:47:25 25.44504 0.2934491 0.11532663 0.2682686 4272.115 9.0475 0.10338978 0.386 0.286 52.0 No No No None Severe None None Yes Normal No Normal, Bilateral 2 2018-10-10 182 days 1 3
42 1787031 7 Female Right ONH 6x6 Angiography 2019-05-08 2019-05-08 11:09:31 25.08622 0.3086875 0.12305063 0.2841450 4433.711 7.5607 0.10895244 0.380 0.278 52.0 No No No None Severe None None Yes Normal No Normal, Bilateral 3 2018-10-10 210 days 1 3
75 2360743 10 Male Left ONH 6x6 Angiography 2018-08-27 2018-08-27 16:11:17 27.78426 0.1930609 0.06948571 0.1805683 2985.314 13.0653 0.06529053 0.291 0.306 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 1 2018-08-27 0 days 1 6
75 2360743 10 Male Left ONH 6x6 Angiography 2019-03-04 2019-03-04 17:12:06 27.87001 0.2087222 0.07489131 0.1947559 3226.429 12.4484 0.06990845 0.302 0.308 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 2 2018-08-27 189 days 1 6
75 2360743 9 Male Left ONH 6x6 Angiography 2019-07-19 2019-07-19 11:00:41 27.48735 0.1704014 0.06199265 0.1601514 2673.694 14.4143 0.05653714 0.297 0.292 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 3 2018-08-27 326 days 1 6
75 2360743 9 Male Left ONH 6x6 Angiography 2019-09-13 2019-09-13 10:16:26 27.08991 0.1727003 0.06375077 0.1614856 2649.738 13.0485 0.05749367 0.293 0.289 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 4 2018-08-27 382 days 1 6
75 2360743 10 Male Left ONH 6x6 Angiography 2019-10-18 2019-10-18 10:00:02 27.46399 0.1728102 0.06292248 0.1616125 2693.818 13.8972 0.05646246 0.304 0.288 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 5 2018-08-27 417 days 1 6
75 2360743 9 Male Left ONH 6x6 Angiography 2019-11-22 2019-11-22 09:52:43 27.16595 0.1915620 0.07051549 0.1791181 2946.412 12.7424 0.06469231 0.299 0.299 63.0 No No No None None Moderate None No Glaucoma No Glaucoma, Bilateral 6 2018-08-27 452 days 1 6
82 35357 10 Female Left ONH 6x6 Angiography 2017-03-16 2017-03-16 15:01:12 24.82872 0.3273775 0.13185434 0.3045946 4978.047 7.0865 0.11088273 0.438 0.331 80.0 No No No None None Mild None Yes Glaucoma No Glaucoma, Bilateral 1 2017-03-16 0 days 1 2
82 35357 10 Female Left ONH 6x6 Angiography 2019-11-06 2019-11-06 09:13:11 24.08127 0.3504950 0.14554675 0.3246427 5449.887 5.5967 0.11861236 0.446 0.338 80.0 No No No None None Mild None Yes Glaucoma No Glaucoma, Bilateral 2 2017-03-16 965 days 1 2
92 51313 8 Female Right ONH 6x6 Angiography 2019-05-03 2019-05-03 14:18:00 27.45707 0.1756779 0.06398276 0.1636341 2803.662 15.9611 0.05454180 0.393 0.262 65.4 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 1 2019-05-03 0 days 1 2
92 51313 10 Female Right ONH 6x6 Angiography 2019-10-04 2019-10-04 13:46:37 25.37820 0.2431212 0.09579924 0.2268217 3792.671 9.7405 0.07838918 0.377 0.296 65.4 No No No None None Severe None No Glaucoma No Glaucoma, Unilateral 2 2019-05-03 154 days 1 2
220 7618939 8 Male Right ONH 6x6 Angiography 2019-09-27 2019-09-27 09:31:48 24.61454 0.3086070 0.12537588 0.2857071 4605.931 6.5831 0.10433904 0.421 0.330 63.9 No No No None Mild None None Yes Normal No Glaucoma, Unilateral 1 2019-09-27 0 days 1 2
220 7618939 9 Male Right ONH 6x6 Angiography 2019-11-01 2019-11-01 10:00:51 24.31144 0.3621905 0.14897947 0.3345446 5352.807 2.8209 0.12682591 0.425 0.358 63.9 No No No None Mild None None Yes Normal No Glaucoma, Unilateral 2 2019-09-27 35 days 1 2
232 7685911 10 Male Left ONH 6x6 Angiography 2019-05-17 2019-05-17 09:36:40 24.43870 0.4260757 0.17434466 0.3894777 6321.509 1.9411 0.15991722 0.456 0.377 41.9 No No No None Mild None None No Normal No Normal, Bilateral 1 2019-05-17 0 days 1 2
232 7685911 7 Male Left ONH 6x6 Angiography 2019-10-25 2019-10-25 09:03:28 24.78055 0.3231436 0.13040208 0.2996570 4879.827 7.5546 0.11223840 0.438 0.328 41.9 No No No None Mild None None No Normal No Normal, Bilateral 2 2019-05-17 161 days 1 2

Reliability, One Eye

Reliability of OCTA Variables

Calculate the within-subject standard deviation \((S_w)\), the within-subject coefficient of repeatability \((CR_w)\), and the within-subject coefficient of variation \((CV_w)\) for a given measurement variable \(x\).

Table 2: Reliability

Table 2 shows Reliability estimates of vessel density measurements.

This table was modeled after Table 2 in Venugopal (2018).2

Intra-Visit Repeatability

Normal

OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 180 24.921 0.240 (0.228, 0.253) 0.665 (0.631, 0.700) 0.963 (0.913, 1.013)
Vessel Area Density 180 0.362 0.014 (0.014, 0.014) 0.038 (0.038, 0.039) 3.832 (3.820, 3.843)
Vessel Area Density, Zeiss 180 0.429 0.006 (0.006, 0.006) 0.016 (0.016, 0.016) 1.369 (1.368, 1.371)
Vessel Skeleton Density (units?) 180 0.146 0.006 (0.006, 0.006) 0.017 (0.017, 0.017) 4.215 (4.210, 4.221)
Vessel Perimeter Index (units?) 180 0.331 0.012 (0.012, 0.012) 0.034 (0.034, 0.034) 3.699 (3.689, 3.709)
Vessel Complexity Index (units?) 180 5379.302 200.808 (-7047.568, 7449.184) 556.611 (-19534.863, 20648.084) 3.733 (-131.013, 138.479)
Flow Impairment Zone (units?) 180 5.037 0.832 (0.615, 1.050) 2.307 (1.704, 2.910) 16.524 (12.203, 20.844)
Flux 180 0.130 0.006 (0.006, 0.006) 0.017 (0.017, 0.017) 4.673 (4.668, 4.679)
Flux, Zeiss 180 0.360 0.007 (0.007, 0.007) 0.018 (0.018, 0.018) 1.847 (1.844, 1.849)

Glaucoma

OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 202 26.249 0.409 (0.368, 0.449) 1.133 (1.020, 1.246) 1.557 (1.402, 1.712)
Vessel Area Density 202 0.278 0.024 (0.024, 0.025) 0.068 (0.067, 0.068) 8.783 (8.684, 8.883)
Vessel Area Density, Zeiss 202 0.397 0.007 (0.007, 0.007) 0.019 (0.019, 0.019) 1.767 (1.765, 1.770)
Vessel Skeleton Density (units?) 202 0.108 0.011 (0.011, 0.011) 0.030 (0.029, 0.030) 9.857 (9.809, 9.904)
Vessel Perimeter Index (units?) 202 0.256 0.022 (0.022, 0.022) 0.061 (0.061, 0.062) 8.657 (8.568, 8.746)
Vessel Complexity Index (units?) 202 4213.362 360.577 (-59387.279, 60108.434) 999.470 (-164613.140, 166612.079) 8.558 (-1409.499, 1426.614)
Flow Impairment Zone (units?) 202 9.250 1.462 (0.777, 2.148) 4.053 (2.153, 5.953) 15.806 (8.396, 23.216)
Flux 202 0.096 0.010 (0.010, 0.010) 0.027 (0.027, 0.027) 10.108 (10.060, 10.156)
Flux, Zeiss 202 0.320 0.007 (0.007, 0.007) 0.019 (0.019, 0.019) 2.119 (2.116, 2.122)

Inter-Visit Reproducibility

Restrict to repeat measurements within a given window of time to minimize differences due to real changes in psychopathology.

Inter-Visit Reproducibility Normal

Normal, All
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 151 24.877 0.341 (0.317, 0.365) 0.946 (0.880, 1.012) 1.372 (1.276, 1.468)
Vessel Area Density 151 0.361 0.024 (0.024, 0.024) 0.067 (0.067, 0.068) 6.724 (6.681, 6.767)
Vessel Area Density, Zeiss 151 0.430 0.009 (0.009, 0.009) 0.026 (0.026, 0.026) 2.166 (2.162, 2.170)
Vessel Skeleton Density (units?) 151 0.146 0.011 (0.011, 0.011) 0.029 (0.029, 0.030) 7.289 (7.269, 7.308)
Vessel Perimeter Index (units?) 151 0.331 0.021 (0.021, 0.021) 0.058 (0.058, 0.058) 6.307 (6.272, 6.342)
Vessel Complexity Index (units?) 151 5357.350 333.268 (-30444.472, 31111.007) 923.771 (-84387.771, 86235.313) 6.221 (-568.275, 580.716)
Flow Impairment Zone (units?) 151 5.136 1.410 (0.884, 1.936) 3.909 (2.451, 5.367) 27.460 (17.217, 37.703)
Flux 151 0.129 0.011 (0.011, 0.011) 0.031 (0.031, 0.031) 8.697 (8.671, 8.722)
Flux, Zeiss 151 0.358 0.012 (0.012, 0.012) 0.032 (0.032, 0.032) 3.259 (3.250, 3.269)
Normal, 365 Days
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 85 24.852 0.371 (0.329, 0.412) 1.027 (0.911, 1.143) 1.491 (1.322, 1.660)
Vessel Area Density 85 0.361 0.022 (0.022, 0.022) 0.062 (0.061, 0.062) 6.155 (6.102, 6.208)
Vessel Area Density, Zeiss 85 0.428 0.008 (0.008, 0.008) 0.023 (0.023, 0.023) 1.961 (1.957, 1.966)
Vessel Skeleton Density (units?) 85 0.146 0.010 (0.010, 0.010) 0.028 (0.028, 0.028) 6.871 (6.846, 6.895)
Vessel Perimeter Index (units?) 85 0.331 0.020 (0.020, 0.020) 0.055 (0.055, 0.056) 6.016 (5.971, 6.061)
Vessel Complexity Index (units?) 85 5337.511 311.185 (-37255.264, 37877.634) 862.561 (-103266.323, 104991.445) 5.830 (-697.989, 709.650)
Flow Impairment Zone (units?) 85 5.070 1.357 (0.683, 2.030) 3.760 (1.894, 5.626) 26.758 (13.478, 40.038)
Flux 85 0.129 0.010 (0.010, 0.010) 0.027 (0.027, 0.027) 7.568 (7.537, 7.598)
Flux, Zeiss 85 0.358 0.010 (0.010, 0.010) 0.029 (0.029, 0.029) 2.900 (2.888, 2.912)
Normal, 180 Days
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 42 24.699 0.407 (0.342, 0.471) 1.127 (0.948, 1.306) 1.647 (1.385, 1.908)
Vessel Area Density 42 0.365 0.029 (0.028, 0.029) 0.079 (0.078, 0.080) 7.822 (7.725, 7.918)
Vessel Area Density, Zeiss 42 0.431 0.009 (0.009, 0.009) 0.024 (0.024, 0.024) 2.040 (2.034, 2.046)
Vessel Skeleton Density (units?) 42 0.148 0.013 (0.013, 0.013) 0.036 (0.035, 0.036) 8.690 (8.647, 8.734)
Vessel Perimeter Index (units?) 42 0.335 0.026 (0.025, 0.026) 0.071 (0.070, 0.072) 7.627 (7.545, 7.708)
Vessel Complexity Index (units?) 42 5436.781 390.390 (-69753.718, 70534.497) 1082.105 (-193347.441, 195511.651) 7.181 (-1282.997, 1297.358)
Flow Impairment Zone (units?) 42 4.602 1.665 (0.418, 2.911) 4.614 (1.159, 8.070) 36.175 (9.084, 63.267)
Flux 42 0.130 0.013 (0.013, 0.013) 0.035 (0.035, 0.035) 9.809 (9.752, 9.866)
Flux, Zeiss 42 0.357 0.014 (0.013, 0.014) 0.038 (0.037, 0.038) 3.790 (3.767, 3.812)

Inter-Visit Reproducibility Glaucoma

Glaucoma, All
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 225 26.456 0.596 (0.532, 0.660) 1.652 (1.475, 1.829) 2.253 (2.012, 2.495)
Vessel Area Density 225 0.268 0.031 (0.031, 0.032) 0.087 (0.086, 0.087) 11.674 (11.569, 11.779)
Vessel Area Density, Zeiss 225 0.392 0.009 (0.009, 0.009) 0.024 (0.024, 0.024) 2.192 (2.189, 2.194)
Vessel Skeleton Density (units?) 225 0.104 0.014 (0.013, 0.014) 0.037 (0.037, 0.038) 13.047 (12.998, 13.097)
Vessel Perimeter Index (units?) 225 0.246 0.028 (0.028, 0.029) 0.079 (0.078, 0.079) 11.535 (11.442, 11.629)
Vessel Complexity Index (units?) 225 4056.458 451.493 (-56816.268, 57719.254) 1251.474 (-157486.660, 159989.608) 11.130 (-1400.637, 1422.898)
Flow Impairment Zone (units?) 225 9.695 1.976 (1.205, 2.747) 5.476 (3.339, 7.613) 20.378 (12.426, 28.330)
Flux 225 0.093 0.013 (0.013, 0.013) 0.036 (0.036, 0.036) 14.001 (13.947, 14.055)
Flux, Zeiss 225 0.317 0.012 (0.012, 0.012) 0.032 (0.032, 0.032) 3.645 (3.639, 3.651)
Glaucoma, 365 Days
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 161 26.627 0.620 (0.546, 0.694) 1.719 (1.514, 1.923) 2.329 (2.051, 2.606)
Vessel Area Density 161 0.260 0.032 (0.032, 0.032) 0.089 (0.088, 0.090) 12.291 (12.155, 12.426)
Vessel Area Density, Zeiss 161 0.390 0.009 (0.009, 0.009) 0.025 (0.025, 0.025) 2.315 (2.312, 2.319)
Vessel Skeleton Density (units?) 161 0.100 0.014 (0.014, 0.014) 0.038 (0.038, 0.038) 13.783 (13.718, 13.848)
Vessel Perimeter Index (units?) 161 0.239 0.029 (0.029, 0.029) 0.081 (0.080, 0.082) 12.169 (12.047, 12.291)
Vessel Complexity Index (units?) 161 3939.684 461.849 (-72837.153, 73760.852) 1280.181 (-201894.289, 204454.651) 11.723 (-1848.807, 1872.253)
Flow Impairment Zone (units?) 161 10.117 2.037 (1.076, 2.998) 5.646 (2.982, 8.311) 20.135 (10.634, 29.636)
Flux 161 0.090 0.013 (0.013, 0.013) 0.036 (0.036, 0.037) 14.641 (14.571, 14.710)
Flux, Zeiss 161 0.314 0.011 (0.011, 0.011) 0.031 (0.031, 0.031) 3.586 (3.579, 3.593)
Glaucoma, 180 Days
OCTA Variable n_measure µ Sw Sw 95% CL CRw CRw 95% CL CVw CVw 95% CL
Vessel Diameter (units?) 115 26.862 0.647 (0.546, 0.747) 1.792 (1.515, 2.070) 2.407 (2.034, 2.780)
Vessel Area Density 115 0.255 0.032 (0.031, 0.032) 0.088 (0.086, 0.089) 12.398 (12.233, 12.563)
Vessel Area Density, Zeiss 115 0.389 0.010 (0.010, 0.010) 0.027 (0.027, 0.027) 2.473 (2.468, 2.477)
Vessel Skeleton Density (units?) 115 0.098 0.014 (0.014, 0.014) 0.038 (0.037, 0.038) 13.927 (13.848, 14.006)
Vessel Perimeter Index (units?) 115 0.235 0.029 (0.029, 0.029) 0.080 (0.079, 0.081) 12.312 (12.163, 12.462)
Vessel Complexity Index (units?) 115 3855.582 460.356 (-91384.759, 92305.471) 1276.041 (-253305.629, 255857.711) 11.940 (-2370.194, 2394.074)
Flow Impairment Zone (units?) 115 10.446 2.149 (0.887, 3.410) 5.956 (2.459, 9.453) 20.570 (8.492, 32.647)
Flux 115 0.089 0.013 (0.013, 0.013) 0.036 (0.036, 0.036) 14.718 (14.634, 14.802)
Flux, Zeiss 115 0.311 0.011 (0.011, 0.011) 0.031 (0.031, 0.031) 3.605 (3.597, 3.614)

Calculating Reliability Statistics

Explanations of reliability statistic calculations

Within-Subject Mean \((\mu_w)\)

\(\mu_w\) is the average of all measurements of one eye for a given individual. The overall mean \((\mu)\) is calculated by taking the mean of \(\mu_w\) across the dataset. The overall mean is included in the final table for reference.

\[ \mu_w = \frac{1}{M}\sum_{i=1}^{M} x_i \]

\[\text{where } M \text{ is the number of measurements per eye,}\]

Within-Subject Standard Deviation \((S_w)\)

Find \(S_w\) by first calculating the variance of the measurements per individual eye. The equation below is general for any number of measurements; in this study there are at least 2 measurements per eye, but sometimes more.

\[ \sigma^2_{measurement} = \frac{1}{M}\sum_{i=1}^{M} (x_i - \mu_w)^2 \]

\[ \text{where } M \text{ is the number of measurements per eye} \]

To calculate \(S_w\), average of the variance of measurements \((\sigma^2_{measurement})\) for all eyes measured, then take the square root.

\[ Sw = \sqrt{\frac{1}{N}\sum_{i=1}^{N}\sigma^2_{measurement,i}} \]

\[ \text{where } N \text{ is the number of eyes measured} \]

Within-Subject Coefficient of Repeatability \((CR_w)\)

The \(CR_w\) provides the uncertainty of repeated measures.

\[ CRw = \sqrt2 * 1.96 * Sw \]

The \(CR_w\) can be interpreted as:

“The difference between two measurements for the same subject is expected to be less than [\(CR_w\)] for 95% of pairs of observations.”3

Within-Subject Coefficient of Variation \((CV_w)\)

\[ CVw = 100 *\frac{Sw}{\mu} \]

ICC, One Eye

Intraclass Correlation Coefficient (ICC) is scored using the ICCest() function from the ICC package. This function “estimates the ICC and confidence intervals using the variance components from a one-way ANOVA.”

ICCest() adjusts for repeat measurements on each participant, but not for repeat measurements on both eyes. Therefore, ICC calculations with this function will be done for data from 1 eye per participant.

This is a preliminary result, as we want to calculate the ICC after adjusting for participant and eye (left or right). This will be done later in the mixed effects regression models.

Intra-Visit ICC, One Eye

Normal

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 68 0.868 (0.807, 0.913) 2.646 0.059 0.385
Vessel Area Density 68 0.910 (0.867, 0.941) 2.646 0.000 0.002
Vessel Area Density, Zeiss 68 0.935 (0.902, 0.957) 2.646 0.000 0.000
Vessel Skeleton Density (units?) 68 0.914 (0.872, 0.943) 2.646 0.000 0.000
Vessel Perimeter Index (units?) 68 0.911 (0.868, 0.942) 2.646 0.000 0.002
Vessel Complexity Index (units?) 68 0.902 (0.855, 0.936) 2.646 40923.407 375866.654
Flow Impairment Zone (units?) 68 0.863 (0.801, 0.909) 2.646 0.696 4.389
Flux 68 0.914 (0.872, 0.944) 2.646 0.000 0.000
Flux, Zeiss 68 0.930 (0.896, 0.954) 2.646 0.000 0.001

Glaucoma

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 81 0.948 (0.924, 0.965) 2.492 0.166 3.028
Vessel Area Density 81 0.905 (0.862, 0.935) 2.492 0.001 0.006
Vessel Area Density, Zeiss 81 0.972 (0.958, 0.981) 2.492 0.000 0.002
Vessel Skeleton Density (units?) 81 0.909 (0.869, 0.939) 2.492 0.000 0.001
Vessel Perimeter Index (units?) 81 0.905 (0.863, 0.936) 2.492 0.001 0.005
Vessel Complexity Index (units?) 81 0.903 (0.860, 0.934) 2.492 145259.846 1347930.822
Flow Impairment Zone (units?) 81 0.877 (0.824, 0.917) 2.492 2.314 16.543
Flux 81 0.898 (0.854, 0.931) 2.492 0.000 0.001
Flux, Zeiss 81 0.965 (0.949, 0.977) 2.492 0.000 0.001

Inter-Visit ICC, One Eye

Inter-Visit ICC Normal

Normal, All

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 67 0.738 (0.620, 0.826) 2.251 0.122 0.344
Vessel Area Density 67 0.765 (0.656, 0.845) 2.251 0.001 0.002
Vessel Area Density, Zeiss 67 0.842 (0.763, 0.897) 2.251 0.000 0.000
Vessel Skeleton Density (units?) 67 0.779 (0.675, 0.855) 2.251 0.000 0.000
Vessel Perimeter Index (units?) 67 0.786 (0.685, 0.859) 2.251 0.000 0.002
Vessel Complexity Index (units?) 67 0.772 (0.665, 0.850) 2.251 114021.925 385838.270
Flow Impairment Zone (units?) 67 0.708 (0.580, 0.805) 2.251 2.001 4.862
Flux 67 0.746 (0.630, 0.831) 2.251 0.000 0.000
Flux, Zeiss 67 0.832 (0.749, 0.891) 2.251 0.000 0.001

Normal, 365 Days

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 40 0.727 (0.553, 0.843) 2.122 0.138 0.367
Vessel Area Density 40 0.801 (0.664, 0.888) 2.122 0.000 0.002
Vessel Area Density, Zeiss 40 0.871 (0.776, 0.928) 2.122 0.000 0.000
Vessel Skeleton Density (units?) 40 0.803 (0.668, 0.889) 2.122 0.000 0.000
Vessel Perimeter Index (units?) 40 0.800 (0.662, 0.887) 2.122 0.000 0.002
Vessel Complexity Index (units?) 40 0.800 (0.662, 0.887) 2.122 96147.110 383611.238
Flow Impairment Zone (units?) 40 0.729 (0.556, 0.844) 2.122 1.858 5.002
Flux 40 0.800 (0.663, 0.887) 2.122 0.000 0.000
Flux, Zeiss 40 0.877 (0.786, 0.932) 2.122 0.000 0.001

Normal, 180 Days

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 19 0.725 (0.455, 0.880) 2.198 0.166 0.437
Vessel Area Density 19 0.674 (0.375, 0.855) 2.198 0.001 0.002
Vessel Area Density, Zeiss 19 0.807 (0.598, 0.918) 2.198 0.000 0.000
Vessel Skeleton Density (units?) 19 0.690 (0.399, 0.863) 2.198 0.000 0.000
Vessel Perimeter Index (units?) 19 0.674 (0.374, 0.855) 2.198 0.001 0.001
Vessel Complexity Index (units?) 19 0.690 (0.399, 0.863) 2.198 148183.011 329773.456
Flow Impairment Zone (units?) 19 0.637 (0.318, 0.836) 2.198 2.723 4.770
Flux 19 0.662 (0.356, 0.849) 2.198 0.000 0.000
Flux, Zeiss 19 0.699 (0.413, 0.867) 2.198 0.000 0.000

Inter-Visit ICC Glaucoma

Glaucoma

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 81 0.897 (0.855, 0.930) 2.77 0.364 3.180
Vessel Area Density 81 0.823 (0.755, 0.877) 2.77 0.001 0.005
Vessel Area Density, Zeiss 81 0.959 (0.940, 0.972) 2.77 0.000 0.002
Vessel Skeleton Density (units?) 81 0.834 (0.769, 0.885) 2.77 0.000 0.001
Vessel Perimeter Index (units?) 81 0.824 (0.756, 0.877) 2.77 0.001 0.005
Vessel Complexity Index (units?) 81 0.829 (0.762, 0.881) 2.77 243669.027 1179265.229
Flow Impairment Zone (units?) 81 0.760 (0.673, 0.831) 2.77 4.352 13.816
Flux 81 0.790 (0.711, 0.852) 2.77 0.000 0.001
Flux, Zeiss 81 0.885 (0.838, 0.921) 2.77 0.000 0.001

Glaucoma, 365 Days

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 62 0.894 (0.840, 0.932) 2.589 0.411 3.448
Vessel Area Density 62 0.821 (0.738, 0.883) 2.589 0.001 0.006
Vessel Area Density, Zeiss 62 0.956 (0.932, 0.972) 2.589 0.000 0.002
Vessel Skeleton Density (units?) 62 0.833 (0.754, 0.891) 2.589 0.000 0.001
Vessel Perimeter Index (units?) 62 0.823 (0.740, 0.884) 2.589 0.001 0.005
Vessel Complexity Index (units?) 62 0.827 (0.746, 0.887) 2.589 258530.328 1237596.013
Flow Impairment Zone (units?) 62 0.760 (0.655, 0.841) 2.589 4.645 14.744
Flux 62 0.785 (0.689, 0.859) 2.589 0.000 0.001
Flux, Zeiss 62 0.895 (0.842, 0.933) 2.589 0.000 0.001

Glaucoma, 180 Days

OCTA Variable n_people ICC ICC 95% CL k varw vara
Vessel Diameter (units?) 48 0.897 (0.834, 0.939) 2.391 0.447 3.896
Vessel Area Density 48 0.850 (0.761, 0.910) 2.391 0.001 0.006
Vessel Area Density, Zeiss 48 0.951 (0.920, 0.971) 2.391 0.000 0.002
Vessel Skeleton Density (units?) 48 0.861 (0.778, 0.917) 2.391 0.000 0.001
Vessel Perimeter Index (units?) 48 0.851 (0.763, 0.910) 2.391 0.001 0.005
Vessel Complexity Index (units?) 48 0.851 (0.763, 0.910) 2.391 241852.820 1380095.308
Flow Impairment Zone (units?) 48 0.773 (0.650, 0.861) 2.391 4.913 16.772
Flux 48 0.821 (0.719, 0.892) 2.391 0.000 0.001
Flux, Zeiss 48 0.909 (0.852, 0.946) 2.391 0.000 0.001

Calculating ICC Statistic

\[ \text{ICC} = \frac{\text{between}}{\text{between} + \text{within}}\]

“In the output for the random effects model ‘SID’ is the estimated between-group variance, which in the ICCest output is called ‘vara’ (variance among groups). The within-group variance is ‘Residual’ in the random effects model output, while in ICCest it’s called ‘varw.’ You can see that the values for those two variances match perfectly in the two different outputs. The ICC is defined as between/(between+within). That calculation is not part of the random effects model output, but it is part of the ICCest output, along with confidence intervals for the ICC estimate. The ICC are really high for intravisit (around 97%) and a little lower for intervisit (about 94%). If we were to calculate these ICC for glaucoma and controls separately I think they would be significantly lower because of the reduced between-group variability.” - BB 9/4/2019

ARVO Abstract Tables, One Eye

Do not use these tables for the final write-up.

Originally, we submitted the abstract to ARVO after calculating reliability statistics on one, randomly selected eye per person. These are kept in the analysis here just to show what we had previously shown. Now, we have calculated these statistics using both eyes (down below). So when writing the final paper, only include those.

Table 1: Participants

Overall
n 149
Sociodemographic Variables
age (mean (SD)) 56.97 (16.10)
Sex = Male (%) 72 (48.3)
Systemic Clinical Variables
Hypertension Diagnosis = Yes (%) 43 (28.9)
Diabetes Mellitus Diagnosis = Yes (%) 17 (11.4)
Optic Neuropathy = Yes (%) 1 ( 0.7)
Ophthalmic Clinical Variables
Glaucoma Diagnosis, Binary = Glaucoma (%) 81 (54.4)
Glaucoma Diagnosis Laterality, Ordinal (%)
Normal, Bilateral 60 (40.3)
Glaucoma, Bilateral 71 (47.7)
Glaucoma, Unilateral 18 (12.1)
Diabetic Retinopathy Diagnosis, Binary = Yes (%) 4 ( 2.7)
Ophthalmic Surgical Variables
Surgical Procedure for Cataract Extraction = Yes (%) 29 (19.5)
Surgical Procedure for Glaucoma (%)
None 106 (71.1)
Laser 24 (16.1)
Minimally Invasive Glaucoma Surgery 1 ( 0.7)
Filter 18 (12.1)
OCT Angiography Signal Strength
signal_strength (mean (SD)) 9.31 (0.75)

Table 2: Reliability Statistics, One Eye

Table 2a: Intra-Visit Repeatability

All data was included for intra-visit repeatability statistics.

Intra-visit repeatability statistics for participants with repeated measurements on the same day:

  • Normal (n = 68).

  • Glaucoma (n = 81).

OCTA Variable
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name_normal µ_normal µ_glc ICC_pretty_normal ICC_pretty_cl_normal ICC_pretty_glc ICC_pretty_cl_glc Sw_pretty_normal Sw_pretty_cl_normal Sw_pretty_glc Sw_pretty_cl_glc CRw_pretty_normal CRw_pretty_cl_normal CRw_pretty_glc CRw_pretty_cl_glc CVw_pretty_normal CVw_pretty_cl_normal CVw_pretty_glc CVw_pretty_cl_glc
Vessel Area Density 0.362 0.278 0.910 (0.867, 0.941) 0.905 (0.862, 0.935) 0.014 (0.014, 0.014) 0.024 (0.024, 0.025) 0.038 (0.038, 0.039) 0.068 (0.067, 0.068) 3.832 (3.820, 3.843) 8.783 (8.684, 8.883)
Vessel Area Density, Zeiss 0.429 0.397 0.935 (0.902, 0.957) 0.972 (0.958, 0.981) 0.006 (0.006, 0.006) 0.007 (0.007, 0.007) 0.016 (0.016, 0.016) 0.019 (0.019, 0.019) 1.369 (1.368, 1.371) 1.767 (1.765, 1.770)
Vessel Skeleton Density (units?) 0.146 0.108 0.914 (0.872, 0.943) 0.909 (0.869, 0.939) 0.006 (0.006, 0.006) 0.011 (0.011, 0.011) 0.017 (0.017, 0.017) 0.030 (0.029, 0.030) 4.215 (4.210, 4.221) 9.857 (9.809, 9.904)
Flux 0.130 0.096 0.914 (0.872, 0.944) 0.898 (0.854, 0.931) 0.006 (0.006, 0.006) 0.010 (0.010, 0.010) 0.017 (0.017, 0.017) 0.027 (0.027, 0.027) 4.673 (4.668, 4.679) 10.108 (10.060, 10.156)
Flux, Zeiss 0.360 0.320 0.930 (0.896, 0.954) 0.965 (0.949, 0.977) 0.007 (0.007, 0.007) 0.007 (0.007, 0.007) 0.018 (0.018, 0.018) 0.019 (0.019, 0.019) 1.847 (1.844, 1.849) 2.119 (2.116, 2.122)

Table 2b: Inter-Visit Reproducibility

Data was restricted to 1 year for inter-visits that occurred on different days. This was to avoid changes in eyes over a long amount of time.

Inter-visit reproducibility statistics for participants with repeated measurements within a 1 year window

  • Normal (n = 40).

  • Glaucoma (n = 62).

OCTA Variable
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name_normal µ_normal µ_glc ICC_pretty_normal ICC_pretty_cl_normal ICC_pretty_glc ICC_pretty_cl_glc Sw_pretty_normal Sw_pretty_cl_normal Sw_pretty_glc Sw_pretty_cl_glc CRw_pretty_normal CRw_pretty_cl_normal CRw_pretty_glc CRw_pretty_cl_glc CVw_pretty_normal CVw_pretty_cl_normal CVw_pretty_glc CVw_pretty_cl_glc
Vessel Area Density 0.361 0.260 0.801 (0.664, 0.888) 0.821 (0.738, 0.883) 0.022 (0.022, 0.022) 0.032 (0.032, 0.032) 0.062 (0.061, 0.062) 0.089 (0.088, 0.090) 6.155 (6.102, 6.208) 12.291 (12.155, 12.426)
Vessel Area Density, Zeiss 0.428 0.390 0.871 (0.776, 0.928) 0.956 (0.932, 0.972) 0.008 (0.008, 0.008) 0.009 (0.009, 0.009) 0.023 (0.023, 0.023) 0.025 (0.025, 0.025) 1.961 (1.957, 1.966) 2.315 (2.312, 2.319)
Vessel Skeleton Density (units?) 0.146 0.100 0.803 (0.668, 0.889) 0.833 (0.754, 0.891) 0.010 (0.010, 0.010) 0.014 (0.014, 0.014) 0.028 (0.028, 0.028) 0.038 (0.038, 0.038) 6.871 (6.846, 6.895) 13.783 (13.718, 13.848)
Flux 0.129 0.090 0.800 (0.663, 0.887) 0.785 (0.689, 0.859) 0.010 (0.010, 0.010) 0.013 (0.013, 0.013) 0.027 (0.027, 0.027) 0.036 (0.036, 0.037) 7.568 (7.537, 7.598) 14.641 (14.571, 14.710)
Flux, Zeiss 0.358 0.314 0.877 (0.786, 0.932) 0.895 (0.842, 0.933) 0.010 (0.010, 0.010) 0.011 (0.011, 0.011) 0.029 (0.029, 0.029) 0.031 (0.031, 0.031) 2.900 (2.888, 2.912) 3.586 (3.579, 3.593)

Mixed Models, Both Eyes

Mixed Effects Regression Models allow random effects for certain variables. This allows us to include multiple measurements from the same person and eye while still satisfying independence.

Figure 1

Here are the Bland Altman Plots for OCTA outcomes in both eyes. The variables of interest are VAD and FLUX for the current algorithm and the Zeiss algorithm. This is an interesting plot to show before explaing the mixed effects model.

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##                 2

Adjusting for Patients

This model has a random effect for the participant ID, which accounts for repeated measurements on the same person. This does not, however, account for measurements on more than one eye per person. Therefore the data was used that randomly selected one eye per participant. Later models will adjust for this.

This should produce the same ICC and other reliability statistics as the ICCest() function in the tables above. These were not calculated out to compare. Just one model is shown for explanation.

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ (1 | ptid)
##    Data: data_octa_global_intra_1eye
## 
## REML criterion at convergence: -1324.1
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -4.6651 -0.3773 -0.0203  0.3606  4.7125 
## 
## Random effects:
##  Groups   Name        Variance  Std.Dev.
##  ptid     (Intercept) 0.0062447 0.07902 
##  Residual             0.0004409 0.02100 
## Number of obs: 382, groups:  ptid, 149
## 
## Fixed effects:
##              Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept) 3.130e-01  6.566e-03 1.477e+02   47.66   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Adjusting for Both Eyes and Patients

Linear, mixed-effects modeling was used to account for repeated measurements on both eyes of each participant. This allows random effects for both the patient and the eye (left or right), allowing us to model the ICC and other reliability statistics without violating independence.

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ (1 | ptid/eyeid)
##    Data: data_octa_global_intra_2eye
## 
## REML criterion at convergence: -2370.7
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -4.8268 -0.3850 -0.0216  0.3809  4.9207 
## 
## Random effects:
##  Groups     Name        Variance  Std.Dev.
##  eyeid:ptid (Intercept) 0.0013947 0.03735 
##  ptid       (Intercept) 0.0050627 0.07115 
##  Residual               0.0004008 0.02002 
## Number of obs: 644, groups:  eyeid:ptid, 244; ptid, 149
## 
## Fixed effects:
##              Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept) 3.118e-01  6.399e-03 1.457e+02   48.73   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1

Table 3: Reliability Statistics, Both Eyes

Table 3a: Both Eyes, Intra-Visit Repeatability

OCTA Variable
N Participants
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name pretty_n_participant_normal pretty_n_participant_glaucoma pretty_mu_normal pretty_mu_glaucoma pretty_icc_normal pretty_icc_cl_normal pretty_icc_glaucoma pretty_icc_cl_glaucoma pretty_sw_normal pretty_sw_cl_normal pretty_sw_glaucoma pretty_sw_cl_glaucoma pretty_crw_normal pretty_crw_cl_normal pretty_crw_glaucoma pretty_crw_cl_glaucoma pretty_cvw_normal pretty_cvw_cl_normal pretty_cvw_glaucoma pretty_cvw_cl_glaucoma
Vessel Area Density 73 86 0.362 0.279 0.924 (0.890, 0.947) 0.914 (0.884, 0.934) 0.015 (0.014, 0.017) 0.024 (0.022, 0.026) 0.042 (0.039, 0.047) 0.066 (0.061, 0.075) 4.214 (3.847, 4.559) 8.602 (7.474, 9.513)
Vessel Area Density, Zeiss 73 86 0.430 0.398 0.935 (0.905, 0.950) 0.971 (0.962, 0.979) 0.006 (0.006, 0.007) 0.007 (0.006, 0.007) 0.018 (0.016, 0.019) 0.018 (0.017, 0.020) 1.471 (1.326, 1.592) 1.670 (1.500, 1.828)
Vessel Skeleton Density (units?) 73 86 0.146 0.108 0.921 (0.887, 0.945) 0.919 (0.889, 0.939) 0.007 (0.006, 0.007) 0.010 (0.009, 0.012) 0.019 (0.017, 0.021) 0.029 (0.027, 0.032) 4.756 (4.336, 5.218) 9.570 (8.814, 10.370)
Flux 73 86 0.130 0.096 0.920 (0.887, 0.942) 0.910 (0.866, 0.934) 0.007 (0.006, 0.008) 0.009 (0.009, 0.010) 0.019 (0.017, 0.021) 0.026 (0.024, 0.030) 5.238 (4.814, 5.714) 9.866 (8.802, 10.779)
Flux, Zeiss 73 86 0.359 0.320 0.942 (0.916, 0.957) 0.959 (0.944, 0.969) 0.007 (0.006, 0.008) 0.007 (0.007, 0.008) 0.020 (0.017, 0.021) 0.020 (0.018, 0.022) 1.978 (1.784, 2.161) 2.258 (2.030, 2.474)

Table 3b: Both Eyes, Inter-Visit Reproducibility

Look at data by different time restrictions, to see if the ICC increases as the window of time shortens.

**I recommend we use the one that restricts to a single year (365 Days), in spite of the singularity warning. I included all possibilities for reference, however.

All

OCTA Variable
N Participants
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name pretty_n_participant_normal pretty_n_participant_glaucoma pretty_mu_normal pretty_mu_glaucoma pretty_icc_normal pretty_icc_cl_normal pretty_icc_glaucoma pretty_icc_cl_glaucoma pretty_sw_normal pretty_sw_cl_normal pretty_sw_glaucoma pretty_sw_cl_glaucoma pretty_crw_normal pretty_crw_cl_normal pretty_crw_glaucoma pretty_crw_cl_glaucoma pretty_cvw_normal pretty_cvw_cl_normal pretty_cvw_glaucoma pretty_cvw_cl_glaucoma
Vessel Area Density 72 86 0.361 0.271 0.816 (0.730, 0.874) 0.819 (0.743, 0.853) 0.024 (0.021, 0.026) 0.035 (0.032, 0.038) 0.067 (0.060, 0.073) 0.098 (0.089, 0.106) 6.689 (5.954, 7.428) 13.043 (11.967, 14.141)
Vessel Area Density, Zeiss 72 86 0.431 0.393 0.872 (0.825, 0.908) 0.951 (0.931, 0.968) 0.009 (0.008, 0.010) 0.009 (0.008, 0.010) 0.025 (0.022, 0.027) 0.024 (0.022, 0.026) 2.058 (1.806, 2.309) 2.232 (2.027, 2.392)
Vessel Skeleton Density (units?) 72 86 0.145 0.105 0.816 (0.750, 0.865) 0.828 (0.767, 0.875) 0.011 (0.010, 0.012) 0.015 (0.014, 0.017) 0.030 (0.026, 0.033) 0.042 (0.039, 0.045) 7.356 (6.527, 8.062) 14.501 (13.435, 15.951)
Flux 72 86 0.129 0.094 0.803 (0.709, 0.850) 0.786 (0.712, 0.843) 0.011 (0.010, 0.012) 0.015 (0.013, 0.016) 0.030 (0.026, 0.034) 0.041 (0.038, 0.045) 8.486 (7.684, 9.574) 15.744 (14.203, 17.260)
Flux, Zeiss 72 86 0.358 0.318 0.850 (0.798, 0.897) 0.894 (0.855, 0.919) 0.012 (0.010, 0.013) 0.012 (0.011, 0.013) 0.032 (0.028, 0.036) 0.032 (0.030, 0.035) 3.276 (2.873, 3.645) 3.689 (3.345, 3.973)

365 Days

## boundary (singular) fit: see ?isSingular
OCTA Variable
N Participants
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name pretty_n_participant_normal pretty_n_participant_glaucoma pretty_mu_normal pretty_mu_glaucoma pretty_icc_normal pretty_icc_cl_normal pretty_icc_glaucoma pretty_icc_cl_glaucoma pretty_sw_normal pretty_sw_cl_normal pretty_sw_glaucoma pretty_sw_cl_glaucoma pretty_crw_normal pretty_crw_cl_normal pretty_crw_glaucoma pretty_crw_cl_glaucoma pretty_cvw_normal pretty_cvw_cl_normal pretty_cvw_glaucoma pretty_cvw_cl_glaucoma
Vessel Area Density 44 67 0.364 0.266 0.793 (0.704, 0.860) 0.838 (0.773, 0.883) 0.024 (0.020, 0.027) 0.034 (0.031, 0.037) 0.067 (0.058, 0.077) 0.094 (0.084, 0.104) 6.608 (5.475, 7.663) 12.691 (11.331, 14.131)
Vessel Area Density, Zeiss 44 67 0.430 0.393 0.859 (0.769, 0.913) 0.955 (0.932, 0.972) 0.009 (0.007, 0.010) 0.009 (0.008, 0.010) 0.024 (0.020, 0.028) 0.024 (0.022, 0.026) 1.996 (1.684, 2.290) 2.191 (1.941, 2.455)
Vessel Skeleton Density (units?) 44 67 0.147 0.103 0.791 (0.669, 0.848) 0.849 (0.783, 0.888) 0.011 (0.009, 0.013) 0.014 (0.013, 0.016) 0.030 (0.025, 0.034) 0.040 (0.036, 0.044) 7.313 (6.056, 8.773) 14.057 (12.494, 15.492)
Flux 44 67 0.131 0.092 0.801 (0.678, 0.879) 0.806 (0.727, 0.864) 0.011 (0.009, 0.012) 0.014 (0.013, 0.016) 0.029 (0.025, 0.033) 0.039 (0.035, 0.043) 8.079 (6.567, 9.712) 15.326 (13.804, 17.218)
Flux, Zeiss 44 67 0.360 0.317 0.864 (0.801, 0.918) 0.913 (0.871, 0.939) 0.011 (0.009, 0.013) 0.011 (0.010, 0.012) 0.031 (0.026, 0.035) 0.030 (0.027, 0.033) 3.095 (2.502, 3.439) 3.429 (3.083, 3.822)

180 Days

## boundary (singular) fit: see ?isSingular
OCTA Variable
N Participants
Mean
ICC
Sw
CRw
CVw
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
Normal
Glaucoma
var_name pretty_n_participant_normal pretty_n_participant_glaucoma pretty_mu_normal pretty_mu_glaucoma pretty_icc_normal pretty_icc_cl_normal pretty_icc_glaucoma pretty_icc_cl_glaucoma pretty_sw_normal pretty_sw_cl_normal pretty_sw_glaucoma pretty_sw_cl_glaucoma pretty_crw_normal pretty_crw_cl_normal pretty_crw_glaucoma pretty_crw_cl_glaucoma pretty_cvw_normal pretty_cvw_cl_normal pretty_cvw_glaucoma pretty_cvw_cl_glaucoma
Vessel Area Density 23 52 0.367 0.264 0.702 (0.486, 0.840) 0.883 (0.807, 0.918) 0.030 (0.023, 0.038) 0.030 (0.026, 0.034) 0.083 (0.065, 0.100) 0.084 (0.075, 0.095) 8.193 (6.097, 9.811) 11.459 (9.826, 12.968)
Vessel Area Density, Zeiss 23 52 0.434 0.394 0.833 (0.690, 0.907) 0.954 (0.932, 0.966) 0.009 (0.007, 0.011) 0.009 (0.008, 0.010) 0.024 (0.019, 0.028) 0.025 (0.022, 0.028) 1.971 (1.557, 2.465) 2.273 (2.034, 2.547)
Vessel Skeleton Density (units?) 23 52 0.149 0.102 0.701 (0.512, 0.833) 0.891 (0.832, 0.926) 0.014 (0.011, 0.017) 0.013 (0.011, 0.015) 0.038 (0.029, 0.046) 0.036 (0.031, 0.040) 9.073 (7.318, 11.147) 12.684 (10.938, 14.644)
Flux 23 52 0.131 0.092 0.718 (0.469, 0.821) 0.864 (0.788, 0.912) 0.013 (0.010, 0.015) 0.012 (0.011, 0.014) 0.036 (0.029, 0.043) 0.034 (0.029, 0.038) 9.871 (8.124, 12.048) 13.525 (11.240, 15.904)
Flux, Zeiss 23 52 0.358 0.315 0.765 (0.570, 0.863) 0.923 (0.875, 0.950) 0.014 (0.011, 0.017) 0.011 (0.010, 0.013) 0.038 (0.030, 0.044) 0.031 (0.028, 0.035) 3.815 (3.140, 4.306) 3.522 (3.103, 3.971)

Signal Strength, Both Eyes

We take for granted that signal strength affects the OCTA outcome variables. But we should still show this formally, as Venugopal 2018 has at the end of their paper.

“Signal strength index values of the scans had a significant effect on the repeatability of OCTA with the vessel density values increasing in scans with higher SSI values.”2

Their result is a simple table of regression estimates for signal strength, shown in the output below. We’re really showing here that SS is important to include as a covariate in measurements that use OCTA.

Linear Mixed Effects Model

This is an example of the LME Model used to calculate coefficients in the table below

## Linear mixed model fit by REML. t-tests use Satterthwaite's method [
## lmerModLmerTest]
## Formula: v_area_density ~ signal_strength + (1 | ptid/eyeid)
##    Data: data_octa_global_intra_2eye
## 
## REML criterion at convergence: -2437.3
## 
## Scaled residuals: 
##     Min      1Q  Median      3Q     Max 
## -5.1815 -0.3513 -0.0318  0.3754  5.2588 
## 
## Random effects:
##  Groups     Name        Variance  Std.Dev.
##  eyeid:ptid (Intercept) 0.0013550 0.03681 
##  ptid       (Intercept) 0.0044108 0.06641 
##  Residual               0.0003494 0.01869 
## Number of obs: 644, groups:  eyeid:ptid, 244; ptid, 149
## 
## Fixed effects:
##                  Estimate Std. Error        df t value Pr(>|t|)    
## (Intercept)     1.601e-01  1.776e-02 5.612e+02   9.016   <2e-16 ***
## signal_strength 1.634e-02  1.798e-03 4.763e+02   9.089   <2e-16 ***
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
## 
## Correlation of Fixed Effects:
##             (Intr)
## sgnl_strngt -0.941

Signal Strength Affects Reliability of OCTA Measurements

Overall

octa_outcome parameter pretty_beta pretty_se pretty_cl pretty_pval
v_area_density signal_strength 0.016 0.002 (0.013, 0.020) 0.000
zeiss_v_area_density signal_strength 0.005 0.001 (0.004, 0.006) 0.000
v_skeleton_density signal_strength 0.007 0.001 (0.005, 0.009) 0.000
flux signal_strength 0.007 0.001 (0.005, 0.008) 0.000
zeiss_flux signal_strength 0.008 0.001 (0.007, 0.009) 0.000

Normal

octa_outcome parameter pretty_beta pretty_se pretty_cl pretty_pval
v_area_density signal_strength 0.013 0.002 (0.009, 0.017) 0.000
zeiss_v_area_density signal_strength 0.005 0.001 (0.003, 0.006) 0.000
v_skeleton_density signal_strength 0.006 0.001 (0.004, 0.007) 0.000
flux signal_strength 0.006 0.001 (0.004, 0.008) 0.000
zeiss_flux signal_strength 0.007 0.001 (0.006, 0.009) 0.000

Glaucoma

octa_outcome parameter pretty_beta pretty_se pretty_cl pretty_pval
v_area_density signal_strength 0.019 0.003 (0.013, 0.025) 0.000
zeiss_v_area_density signal_strength 0.005 0.001 (0.003, 0.006) 0.000
v_skeleton_density signal_strength 0.008 0.001 (0.005, 0.011) 0.000
flux signal_strength 0.007 0.001 (0.005, 0.009) 0.000
zeiss_flux signal_strength 0.008 0.001 (0.006, 0.010) 0.000

References

1. Venugopal JP, Rao HL, Weinreb RN, et al. Repeatability and comparability of peripapillary vessel density measurements of high-density and non-high-density optical coherence tomography angiography scans in normal and glaucoma eyes. The British Journal of Ophthalmology 2019;103:949–954.

2. Venugopal JP, Rao HL, Weinreb RN, et al. Repeatability of vessel density measurements of optical coherence tomography angiography in normal and glaucoma eyes. The British Journal of Ophthalmology 2018;102:352–357.

3. Bland JM, Altman DG. Statistics Notes: Measurement error. BMJ : British Medical Journal 1996;313:744.